Diacerein is safe and effective for reducing osteoarthritis-associated pain, and its effects persisted for at least 3 months after treatment was stopped in a randomized, double-blind, placebo-controlled, multi-center study.
The anthraquinone derivative is approved for use in several European countries but not in the United States.
An intent-to-treat analysis was carried out on 165 patients randomized to receive 50-mg diacerein capsules (82 patients) or placebo twice daily for 3 months. Most patients had bilateral knee OA, and most were taking nonsteroidal anti-inflammatory drugs. The majority were female and the mean duration of OA was 6.5 years (Arthritis Rheum. 2007;56:4055-64).
The two primary end points were the percentage change in baseline pain as recorded on a 100-mm visual analog scale (VAS) in section A of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and change in score on the total WOMAC from baseline to the fifth month.
“Diacerein showed statistically significant superiority over placebo (P less than .0001) for the primary efficacy criterion,” wrote Dr. Karel Pavelka, of Charles University, Prague, and his associates. Changes in pain on a 100-mm normalized scale were “already significantly different in favor of diacerein at month 2” and the level of pain “decreased further in the diacerein group by the end of treatment (month 3) (P = .0006) and persisted at this level not only at months 4 and 5 … but also at month 6.”
The absolute change in pain at month 3 for the treatment group was 21.6 mm, versus 9.4 mm in the placebo group. At month 5, the treatment group change persisted, at 23.3 mm, versus 9.5 mm in the placebo group.
The other primary end point—change on the total WOMAC—“was also significantly different (P less than .0001) compared with placebo at month 5,” wrote the investigators. The total WOMAC score at baseline was 1,251 and 1,183 in the diacerein and placebo groups, respectively. The diacerein group's score dropped to 834 at month 3 versus 982 in the placebo group, and diacerein patients had a total score of 733 at month 6 versus 1,011 for placebo patients (P = .0045 at month 3 and P less than .0001 at month 6).
A former consultant for Negma, a French company that marketed the drug, Dr. Roy Altman said in an interview that the drug was put before the Food and Drug Administration several times in the last decade. But the “shifting sands” of the agency's clinical trial data requirements prevented the drug from ever gaining approval. (A representative from the FDA's Center for Drug Evaluation and Research would not comment on drugs that had not been approved.)
The Osteoarthritis Research Society International's new therapeutic guidelines are likely to give “approval for diacerein for OA, but not a high recommendation,” according to Dr. Altman, a visiting professor in the division of rheumatology of the University of California, Los Angeles.
The study was supported by a joint grant from TRB Chemedica International SA and Glynn Brothers Chemicals AG, two Switzerland-based companies.
Unpublished international guidelines likely will approve the use of diacerein for OA pain. DR. ALTMAN